Inhibition of estrogen receptor positive and negative breast cancer cell lines with a growth hormone-releasing hormone antagonist.
GHRH antagonists have been shown to inhibit growth of various human cancer cell lines xenografted into nude mice including estrogen receptor negative human breast cancers. Previous observations also suggest that GHRH locally produced in diverse neoplasms including breast cancer might directly affect proliferation of tumor cells. In the present study we demonstrate that a novel highly potent GHRH antagonist JMR-132 strongly inhibits the proliferation of both estrogen receptor negative SKBR 3 and estrogen receptor positive ZR 75 human breast cancer cell lines in vitro. The proliferation in vitro of ZR 75 and SKBR 3 was increased after direct stimulation with GHRH(1-29)NH2. The GHRH antagonist JMR-132 had a significant antiproliferative activity in the absence of GHRH and nullified the proliferative effect of GHRH in these cell lines. SKBR 3 and ZR 75 expressed the GHRH ligand as well as the pituitary type of GHRH-receptor, which likely appears to mediate the antiproliferative mechanisms in these cell lines. These in vitro results suggest that JMR-132 is a potent inhibitor of breast cancer growth, independent of the estrogen receptor status. Further investigations on the combination treatment with endocrine agents affecting the estrogen pathway and GRHR antagonists are needed in order to improve the treatment of breast cancer.
Seitz
Stephan
S
Veterans Affairs Medical Center Miami, FL 33125, USA.
Hohla
Florian
F
Schally
Andrew V
AV
Moder
Angelika
A
Engel
Joerg B
JB
Horn
Felicitas
F
Varga
Josef
J
Zarandi
Marta
M
Ortmann
Olaf
O
Köster
Frank
F
Buchholz
Stefan
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017337:Sermorelin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; C534070:GHRH(1-29)NH2, PhAcTyr(1)-Arg(2)-P(H)e(4-CL)(6)-Ala(8)-Tyr(Me)(10)-His(11)-Abu(15)-His(20)-Nle(27)-Arg(28)-HLCr(29)-; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone